S Jamal MustafaI is the Professor of Pharmacology at West Virginia University School of Medicine and a Senior Advisor to the Pilot Core of the West Virginia Clinical Science and Transla onal Ins tute. He served as an Assistant Dean for Research and the Health Sciences Center from 2005-15. He has received Dean’s Award for Excellence in Research from School of Medicine in 2008 and became a Robert C. Byrd Professor in 2010. In addi on, he received Chancellor’s Award for Outstanding Achievement in Research and Scholarly Ac vi es from HSC in 2013. He has published over 200 manuscripts. Prof. Jamal and the coworker’s past work have led to the approval of an A2A selec ve AR agonist (Lexican®) for myocardial perfusion imaging. Currently, they are using AR and β adrenergic receptor KOs to be er understand the rela onship between these receptors in coronary fl ow regula on.

 

Adenosine acts through its receptors (A1, A2A, A2B, and A3) via G-proteins and causes an increase in coronary fl ow (CF) mostly through A2A AR. However, the role of other ARs in the modula on of CF is not well understood. Using KOs, we inves gated the role for each AR in the regula on of CF. Using the isolated heart from A3 KO mice; we reported an increase in A2A-mediated CF.  Similarly, we found an increase in CF in A1 KO mice with A2A agonist (CGS-21680). Also, in A2A KO mice, response to CGS was abolished. On the other hand, A2A KO mice showed a decrease in CF to NECA (non-selec ve agonist). BAY60-6583 (A2B selec ve agonist) was without an eff ect on CF in A2B KO mice; however, it increased CF signifi cantly in A2A KO. CGS also 

caused a signifi cant increase in CF in A2B KO mice. Also, exogenous adenosine-induced increase in CF in WT, A2A KO, and A2B KO mice were signifi cantly reduced with catalase. BAY-induced increase in CF in WT was signifi cantly inhibited with glibenclamide. Overall, our data support s mulatory roles for A2A and A2B and inhibitory roles for A1 and A3 in the regula on of CF.  These observa ons provide new evidence for the presence of all four ARs in CF regula on. We propose, that ac va on of A2A/B may release H2O2 which then ac vates KATP channels, leading to vasodila on. These studies may lead to be er understanding of the role of ARs in coronary disease and may lead to be er therapeu c approaches.